A peptide having a group, in the molecule, which is capable of being labeled with a metal can be used as an active ingredient in diagnostic or therapeutic agents by labeling the peptide with a radioactive metal, a paramagnetic metal, or the like.
The solubility of a peptide capable of being labeled with a metal decreases in an aqueous solvent with the increase in the number of hydrophobic moieties such as an alkyl group in the peptide structure. A conventional approach to dissolve such a peptide in the aqueous solvent is as follows: the peptide is dissolved in advance in an organic solvent such as dimethylsulfoxide (DMSO), dimethylformamide (DMF); and then the resulting solution is mixed with a required amount of water or a buffer solution or an aqueous solution of a certain substance. For example, formyl-Met-Leu-Phe (FMLP), one of peptides, is known to be poorly soluble in a neutral buffer solution. To dissolve the compound formyl-Met-Leu-Phe-Lys-hydrazinonicotinamide (fMLFK-HYNIC), which is a derivative of the compound FMLP to make it possible to be labeled with a metal, in an aqueous solvent, fMLFK-HYNIC is required to be dissolved with DMSO, followed by adding a necessary buffer solution or aqueous solvent (see Non-Patent Document 1).
However, in the dissolution by the above-described method, upon mixing with the aqueous solvent, the proportion of the organic solvent, which is capable of dissolving the compound, decreases in the solution. When the organic solvent falls short of a certain concentration, sometimes the peptide may become insoluble such as white turbidity and deposition.
As described above, the peptide capable of being labeled with a metal can be used as a nuclear medicine preparation by labeling it with a radioactive metal. Previous applications of dissolution of the above-described peptide with an organic solvent such as DMSO have required reaction conditions of heating at 100° C. for more than 10 minutes or reaction conditions at room temperature for more than 30 minutes for the labeling.
For example, the labeling of the fMLFK-HYNIC requires reaction conditions at room temperature for a period of 30 to 60 minutes (see Non-Patent Document 1).
Peptide derivatives of FMLP are said to be useful in the imaging of disease with leukocyte infiltration such as inflammation, while conditions under which they are capable of being labeled with a metal at room temperature in a completely aqueous solvent are unknown (see Non-Patent Document 2).
Non-Patent Document 1: van der Laken, C J. et al., J. Nucl. Med., 38, 8, 1310-1315 (1997)
Non-Patent Document 2: Verbeke, K. et al., Nuclear Medicine & Biology, Vol. 27, 769-779 (2000)